DOCSLIB.ORG

Virus-Driven Carcinogenesis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

cancers Review Virus-Driven Carcinogenesis Yuichiro Hatano 1,* , Takayasu Ideta 2,3, Akihiro Hirata 4, Kayoko Hatano 5, Hiroyuki Tomita 1 , Hideshi Okada 6 , Masahito Shimizu 2 , Takuji Tanaka 7 and Akira Hara 1 1 Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; [email protected] (H.T.); [email protected] (A.H.) 2 Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; [email protected] (T.I.); [email protected] (M.S.) 3 Department of Laboratory Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan 4 Laboratory of Veterinary Pathology, Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1194, Japan; [email protected] 5 Department of Obstetrics and Gynecology, Gifu University Hospital, Gifu 501-1194, Japan; [email protected] 6 Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; [email protected] 7 Department of Diagnostic Pathology (DDP) and Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, Gifu 500-8513, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-58-230-6225 Simple Summary: Carcinogens, causes of cancer, are usually invisible and therefore in vivo carcino- genesis is difficult to detect. Tumor viruses, definitive carcinogens, are also usually unremarkable, particularly due to latent infection. However, recent developments in tumor virology are unraveling how a single infected cell becomes a life-threatening cell population from a molecular perspective. The recognition and characterization of virus-driven carcinogenesis is the first step in the eradication of tumor virus-associated cancer. Citation: Hatano, Y.; Ideta, T.; Hirata, A.; Hatano, K.; Tomita, H.; Okada, H.; Abstract: Cancer arises from the accumulation of genetic and epigenetic alterations. Even in the era Shimizu, M.; Tanaka, T.; Hara, A. of precision oncology, carcinogens contributing to neoplastic process are still an important focus of Virus-Driven Carcinogenesis. Cancers research. Comprehensive genomic analyses have revealed various combinations of base substitutions, 2021, 13, 2625. https://doi.org/ referred to as the mutational signatures, in cancer. Each mutational signature is believed to arise 10.3390/cancers13112625 from specific DNA damage and repair processes, including carcinogens. However, as a type of carcinogen, tumor viruses increase the cancer risk by alternative mechanisms, including insertional Academic Editor: Karl Munger mutagenesis, viral oncogenes, and immunosuppression. In this review, we summarize virus-driven carcinogenesis to provide a framework for the control of malignant cell proliferation. We first provide Received: 30 April 2021 Accepted: 25 May 2021 a brief overview of oncogenic viruses and describe their implication in virus-related tumors. Next, Published: 27 May 2021 we describe tumor viruses (HPV, Human papilloma virus; HBV, Hepatitis B virus; HCV, Hepatitis C virus; EBV, Epstein–Barr virus; Kaposi sarcoma herpesvirus; MCV, Merkel cell polyoma virus; Publisher’s Note: MDPI stays neutral HTLV-1, Human T-cell lymphotropic virus, type-1) and tumor virus-related cancers. Lastly, we with regard to jurisdictional claims in introduce emerging tumor virus candidates, human cytomegalovirus (CMV), human herpesvirus-6 published maps and institutional affil- (HHV-6) and adeno-associated virus-2 (AAV-2). We expect this review to be a hub in a complex iations. network of data for virus-associated carcinogenesis. Keywords: tumor virus; HPV; HBV; HCV; EBV; KSHV; MCV; HTLV-1; HIV-1 Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article 1. Introduction distributed under the terms and Cancer is classified as a cell proliferative lesion according to its histology and pri- conditions of the Creative Commons mary site. However, cancer frequently shows variation among individuals and unique Attribution (CC BY) license (https:// histological features, and no single histological type is identical to the others. Consistent creativecommons.org/licenses/by/ with this notion, next-generation sequencing-based genomic analyses have shown that 4.0/). Cancers 2021, 13, 2625. https://doi.org/10.3390/cancers13112625 https://www.mdpi.com/journal/cancers Cancers 2021, 13, 2625 2 of 27 each histological cancer type shows intertumoral heterogeneity owing to genomic and epigenomic alterations in cancer-related genes. Such comprehensive analyses clarify not only the status of established cancer-related genes but also collateral factors, including tumor mutational burden and microsatellite instability. These additional factors are closely associated with past DNA damage and repair responses in cancer and play an important role in deciding optimal molecular therapies. These comprehensive analyses allow us to understand individual cancer in a chronological framework and, thus, the molecular classification of cancer is an emerging area in research and healthcare [1]. Will the emerging genomic classification really be the best and only approach in clinical oncology? Another approach for the classification of cancer is to investigate possible predisposing factors. These factors can be hereditary elements [2] and environmental factors, called carcinogens. Among carcinogens, oncogenic viruses predispose carriers to specific types of cancer in infected cells. Of note, studies of virus-driven carcinogenesis have generated insight into oncogenes [3] and thereby to carcinogenesis. Oncogenic viruses are a promising target for cancer prevention, diagnosis, and therapy. In this review, we summarize virus-driven carcinogenesis to understand the malignant cell proliferation as controllable. We initially provide brief remarks on human viruses and oncogenic viruses. Next, we provide a detailed overview of every established virus-driven carcinogenesis. Lastly, we introduce miscellaneous infectious agents, including emerging tumor virus candidates. 2. Overview of Tumor Viruses Inorganic particles that are infectious to humans, called human viruses, were discov- ered at beginning of the 20th century [4]. Despite possessing genetic information like other organisms, viruses fail to self-replicate. Viral replication requires an environmental factor, i.e., an appropriate host cell. Occasionally, virus activity leads to the illness and death of the host, resembling many ecological interactions. Owing to extensive research, the current virus taxonomy is highly complex and is beyond the scope of this review [5]; accordingly, we focus on the relationships between cancer and tumor viruses. Tumor viruses, also called oncogenic viruses or oncoviruses, are associated with one- ninth of cancer cases worldwide [6–9]. As summarized in Table1, principal oncogenic viruses can be classified into six families. The International Agency for Research on Cancer (IARC) recognizes several tumor viruses as human carcinogens [10,11]. Hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein–Barr virus (EBV), Kaposi sarcoma herpesvirus (KSHV), human papilloma viruses (HPVs), especially type 16, and human T-cell lym- photropic virus, type-1 (HTLV-1) are classified as “carcinogenic to humans“ (Group 1) [10]. Polyoma viruses were later added to the IARC monograph series. Merkel cell polyoma virus (MCV) is classified as “probably carcinogenic to humans” (Group 2A); BK virus and JC virus are classified as “possibly carcinogenic to humans” (Group 2B); SV40 virus is regarded as “not classifiable as to its carcinogenicity to humans”(Group 3) [11]. Recently, evidence for the carcinogenicity of MCV has accumulated [12]. Cancers 2021, 13, 2625 3 of 27 Table 1. Summary of human tumor viruses. Variable HPV HBV HCV EBV KSHV MCV HTLV-1 Kaposi Human Human Epstein–Barr Merkel Cell Full Name/ Hepatitis B Hepatitis C Sarcoma T-cell Lym- Papilloma Virus/ Polyoma synonym Virus Virus Herpes photrophic Virus HHV-4 Virus Virus/HHV-8 Virus, type-1 Family Papillomaviridae Hepadnaviridae Flaviviridae Herpesviridae Herpesviridae Polyomaviridae Retroviridae Baltimore Class I Class VII Class IV Class I Class I Class I Class VI System 1 Virus dsDNA ss/dsDNA +ssRNA lineardsDNA circulardsDNA dsDNA +RNA Genome Genome 8 kbp 3 kb/kbp 9.5–12.5 kb 170 kbp 170 kbp 5.4 kbp 9 kbp Size Virion 52–60 nm 52–55 nm 40–60 nm 200 nm 100–150 nm 40–55 nm 100 nm Size Envelope Absent Present Present Present Present Absent Present Capsid Icosahedral Icosahedral Icosahedral Icosahedral Icosahedral Icosahedral Icosahedral Vaccination Accessible Accessible Inaccessible Inaccessible Inaccessible Inaccessible Inaccessible Anti-viral Not Occasionally Not Not Not Effective Effective treatment established Effective established established established Diagnostic anti-HCV p16 HBs antigen EBER LANA CM2B4 ATLA molecule antibody 1 The details of Baltimore system are found in refs. [13,14]. Abbreviations: ATLA, anti-adult T-cell leukemia/lymphoma antibody; ds, double strands; EBER, EBV-encoded small RNA; LANA, Latency-associated nuclear antigen; ss, single strand; +, positive sense. Evidence for virus-driven carcinogenesis is summarized as follows [15]: the existence of viral DNA in tumor tissues, transformation by viral genes in model systems, generation of a neoplastic phenotype in response to the persistent expression of a vital oncogene or modification of host genes, and epidemiological data indicating that viral infections represent
Recommended publications
  • Meat, Fish and Dairy Products and the Risk of Cancer: a Summary Matrix 7 2

    Meat, Fish and Dairy Products and the Risk of Cancer: a Summary Matrix 7 2

    Meat, fish and dairy products and the risk of cancer 2018 Contents World Cancer Research Fund Network 3 Executive summary 5 1. Meat, fish and dairy products and the risk of cancer: a summary matrix 7 2. Summary of Panel judgements 9 3. Definitions and patterns 11 3.1 Red meat 11 3.2 Processed meat 12 3.3 Foods containing haem iron 13 3.4 Fish 13 3.5 Cantonese-style salted fish 13 3.6 Grilled (broiled) or barbecued (charbroiled) meat and fish 14 3.7 Dairy products 14 3.8 Diets high in calcium 15 4. Interpretation of the evidence 16 4.1 General 16 4.2 Specific 16 5. Evidence and judgements 27 5.1 Red meat 27 5.2 Processed meat 31 5.3 Foods containing haem iron 35 5.4 Fish 36 5.5 Cantonese-style salted fish 37 5.6 Grilled (broiled) or barbecued (charbroiled) meat and fish 40 5.7 Dairy products 41 5.8 Diets high in calcium 51 5.9 Other 52 6. Comparison with the 2007 Second Expert Report 52 Acknowledgements 53 Abbreviations 57 Glossary 58 References 65 Appendix 1: Criteria for grading evidence for cancer prevention 71 Appendix 2: Mechanisms 74 Our Cancer Prevention Recommendations 79 2 Meat, fish and dairy products and the risk of cancer 2018 WORLD CANCER RESEARCH FUND NETWORK Our Vision We want to live in a world where no one develops a preventable cancer. Our Mission We champion the latest and most authoritative scientific research from around the world on cancer prevention and survival through diet, weight and physical activity, so that we can help people make informed choices to reduce their cancer risk.
  • Evaluation of the Frequency of Patients with Cancer Presenting to an Emergency Department

    Evaluation of the Frequency of Patients with Cancer Presenting to an Emergency Department

    ORIGINAL ARTICLE Evaluation of the frequency of patients with cancer presenting to an emergency department Cem Isikber1 Muge Gulen1 Salim Satar2 Akkan Avci1 Selen Acehan1 Gulistan Gul Isikber3 Onder Yesiloglu1 1. Adana City Training and Research Hospital, Department of Emergency Medicine, Adana, Turkey. 2. Associate Professor, Adana City Training and Research Hospital, Department of Emergency Medicine, Adana, Turkey. 3. Adana City Training and Research Hospital, Department of Infectious Diseases and Microbiology, Adana, Turkey. http://dx.doi.org/10.1590/1806-9282.66.10.1402 SUMMARY OBJECTIVE: This study aims to determine the demographic characteristics of cancer patients admitted to an emergency department and determine the relationship between the frequency of admission to the emergency department and oncological emergencies and their effect on mortality. METHODS: This observational, prospective, diagnostic accuracy study was performed in the ED of a tertiary care hospital. Patients over the age of 18 who were previously diagnosed with cancer and admitted to the emergency service for medical reasons were included in the study. We recorded baseline characteristics including age, gender, complaints, oncological diagnosis, metastasis status, cancer treatments received, the number of ED admissions, structural and metabolic oncological emergency diagnoses in the ED, discharge status, length of hospital stay, and mortality status. RESULTS: In our study, 1205 applications related to the oncological diagnosis of 261 patients were examined. 55.6% of the patients were male, and 44.4% were female. The most common metabolic oncological emergency was anemia (19.5%), and the most common structural oncological emergency was bone metastasis-fracture (4.6%.) The mean score of admission of patients to the emergency department was four times (min: 1 max: 29) during the study period.
  • ORIGINAL ARTICLE Short Telomeres and High Telomerase Activity in T

    ORIGINAL ARTICLE Short Telomeres and High Telomerase Activity in T

    Leukemia (2007) 21, 2456–2462 & 2007 Nature Publishing Group All rights reserved 0887-6924/07 $30.00 www.nature.com/leu ORIGINAL ARTICLE Short telomeres and high telomerase activity in T-cell prolymphocytic leukemia ARo¨th1,JDu¨rig1, H Himmelreich2,3, S Bug4, R Siebert4,UDu¨hrsen1, PM Lansdorp5,6 and GM Baerlocher2,3 1Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; 2Department of Hematology, University Hospital, Bern, Switzerland; 3Department of Clinical Research, University Hospital, Bern, Switzerland; 4Institute of Human Genetics, Christian-Albrechts-University Hospital Schleswig-Holstein, Kiel, Germany; 5Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, Canada and 6Department of Medicine, University of British Columbia, Vancouver, Canada 4 5 To test the role of telomere biology in T-cell prolymphocytic repeats of the sequence T2AG3 and associated proteins folded leukemia (T-PLL), a rare aggressive disease characterized by into a telomere loop structure.6 Telomeres are required to the expansion of a T-cell clone derived from immuno-compe- tent post-thymic T-lymphocytes, we analyzed telomere length maintain chromosomal integrity and prevent end-to-end fusions and telomerase activity in subsets of peripheral blood leuko- of chromosomes. When telomeric ends become too short, DNA cytes from 11 newly diagnosed or relapsed patients with damage signals from telomeres can induce apoptosis or a state sporadic T-PLL. Telomere length values of the leukemic T cells of replicative senescence.7,8 Telomeres shorten with each round (mean7s.d.: 1.5370.65 kb) were all below the 1st percentile of of cell division as a result of failure to completely replicate the 30 telomere length values observed in T cells from healthy age- end of chromosomes9,10 as well as other causes.11 The average matched controls whereas telomere length of normal T- and telomere length in cells from most human tissues decreases with B cells fell between the 1st and 99th percentile of the normal 12,13 distribution.
  • A Study on Tumor Suppressor Genes Mutations Associated with Different Pppathologicalpathological Cccolorectalcolorectal Lllesions.Lesions

    A Study on Tumor Suppressor Genes Mutations Associated with Different Pppathologicalpathological Cccolorectalcolorectal Lllesions.Lesions

    A Study on Tumor Suppressor Genes Mutations Associated with Different PPPathologicalPathological CCColorectalColorectal LLLesions.Lesions. Thesis Submitted for partial fulfillment of the requirements for the Ph.D. degree of Science in Biochemistry By Salwa Naeim Abd ElEl----KaderKader Mater M.Sc. in Biochemistry, 2002 Biological Applications Department Nuclear Research Center Atomic Energy Authority Under the supervision of Prof. Dr. Amani F.H Nour El ---Deen Prof. Dr. Abdel Hady Ali Abdel Wahab Professor of Biochemistry Professor of Biochemistry Biochemistry Department and Molecular Biology Faculty of Science Cancer Biology Department Ain Shams University National Cancer Institute Cairo University Prof. DrDr.MohsenMohsen Ismail Mohamed Dr. Azza Salah Helmy Professor of Clinical Pathology Biological Assistant Professor of Biochemistry Applications Department Biochemistry Department Nuclear Research Center Faculty of Science Atomic Energy Authority Ain Shams University 2012011111 ﺑﺴﻢ ﺍﷲ ﺍﻟﺮﺣﻤﻦ ﺍﻟﺮﺣﻴﻢ ﺇِﻧﻤﺎ ﺃﹶﻣﺮﻩ ﺇِﺫﹶﺍ ﺃﹶﺭﺍﺩ ﺷﻴﺌﹰﺎ ﺃﹶﹾﻥ ﻳﹸﻘﻮﻝﹶ ﻟﹶﻪ ﻛﹸـﻦ ﻓﹶﻴﻜﹸـﻮ ﻥ ﹸ ””” ٨٢٨٨٢٢٨٢““““ﻓﹶﺴﺒﺤﺎﻥﹶ ﺍﱠﻟﺬِﻱ ﺑِﻴﺪِﻩِ ﻣﻠﹶﻜﹸﻮﺕ ﻛﹸـﻞﱢ ﺷـﻲﺀٍ ﻭﺇِﻟﹶﻴـﻪِ ﺗﺮﺟﻌﻮﻥﹶ ””” ٨٣٨٨٣٣٨٣““““ ﺻﺪﻕ ﺍﷲ ﺍﻟﻌﻈﻴﻢ رة (٨٢-٨٣) I declare that this thesis has been composed by myself and the work there in has not been submitted for a degree at this or any other university. Salwa Naeim Abd El-Kader Matter To my dear husband and family Their love, encouragement and help made my studies possible and to them I owe everything. Thank you Salwa Naeim Abd El-Kader Matter Acknowledgement First of all, thanks to Allah the most merciful for guiding me and giving me the strength to complete this work. It is pleasure to express my deepest thanks and profound respect to Prof.
  • Environmental Causes of Cancer

    Environmental Causes of Cancer

    British Toxicology Society http://www.thebts.org/ Environmental Causes of Cancer What is cancer? Cancer is the uncontrolled replication of cells. Such cells have different characteristics from regular cells, enabling them to escape the normal mechanisms controlling cell division and fate. Cancer develops when cells progressively acquire several of these characteristics. Cancer is a major cause of morbidity and mortality throughout the world. During their lifetime, approximately 50% of the population will develop cancer and, globally, almost 17% will die of cancer. Cancer is spoken of as if it were a single disease, but it is a multiplicity of diseases, each with its own aetiology, risk factors and population trends. Nevertheless, amongst adverse health effects, it is amongst those diseases treated with most dread, not surprisingly given that some forms of cancer are untreatable and have a very high mortality rate. Cancer is a progressive and persistent disease and it typically takes approx. 25% of a lifespan to develop cancer in a solid tissue, such as the liver or lung. A corollary of this is that most cancers are diseases of older age, and almost 50% of cancer deaths are in the over 70s. Hence, as the population ages, the proportion dying of cancer increases. This, in part, reflects the effectiveness of improving population longevity. Given the above, there has been intense focus over the last 50 years in trying to identify the causes of cancer, in that prevention would be the most effective public health strategy. Early studies concluded that the majority of cancer was environmental in origin and some inferred that this was because of the presence of chemicals in the environment, whereas in fact it meant that most cancers were not obviously inherited, i.e.
  • S Sarcoma-Associated Herpesvirus Lana2 Protein Interacts with the Pocket Proteins and Inhibits Their Sumoylation

    S Sarcoma-Associated Herpesvirus Lana2 Protein Interacts with the Pocket Proteins and Inhibits Their Sumoylation

    Oncogene (2014) 33, 495–503 & 2014 Macmillan Publishers Limited All rights reserved 0950-9232/14 www.nature.com/onc ORIGINAL ARTICLE Kaposi’s sarcoma-associated herpesvirus lana2 protein interacts with the pocket proteins and inhibits their sumoylation L Marcos-Villar1,5, P Gallego1,5, C Mun˜ oz-Fontela2, CF de la Cruz-Herrera1, M Campagna1, D Gonza´lez1, F Lopitz-Otsoa3, MS Rodrı´guez3,4 and C Rivas1 The pocket proteins retinoblastoma protein (pRb), p107 and p130 are the key targets of oncoproteins expressed by DNA tumor viruses. Some of these viral proteins contain an LXCXE motif that mediates the interaction with the three pocket proteins and the inhibition of the pRb SUMOylation. Kaposi’s sarcoma herpesvirus (KSHV) contains at least two proteins that can regulate pRb function but, so far, a KSHV-encoded protein targeting p107 and p130 has not been identified. Here, we show that the KSHV latent protein LANA2 binds to pRb, p107 and p130. LANA2 contains an LXCXE motif that is required for bypassing pRb-mediated cell-cycle arrest and for inhibiting pRb SUMOylation. Finally, we demonstrate that, in addition to pRb, both p107 and p130 can be SUMOylated, and this modification is also inhibited by LANA2 in an LXCXE-dependent manner. These results demonstrate, for the first time, the SUMOylation of p107 or p130 and, so far, they represent the first example of a KSHV protein able to interact with the three pocket proteins and to inhibit their conjugation to SUMO. Oncogene (2014) 33, 495–503; doi:10.1038/onc.2012.603; published online 14 January 2013 Keywords: pocket proteins; KSHV; LANA2; pocket proteins; sumoylation; LXCXE domain INTRODUCTION vIRF3, interacts with pRb, p130 and p107 in vitro and in vivo.
  • THE NANOARCHITECTURE of the KSHV LANA TETHER and APPROACHES to ITS DISRUPTION Margaret Josephine Grant Shelton, CT B.S., Brown U

    THE NANOARCHITECTURE of the KSHV LANA TETHER and APPROACHES to ITS DISRUPTION Margaret Josephine Grant Shelton, CT B.S., Brown U

    THE NANOARCHITECTURE OF THE KSHV LANA TETHER AND APPROACHES TO ITS DISRUPTION Margaret Josephine Grant Shelton, CT B.S., Brown University, 2007 A Dissertation presented to the Graduate Faculty of the University of Virginia in Candidacy for the degree of Doctor of Philosophy Department of Microbiology, Immunology, and Cancer Biology University of Virginia May 2018 _____________________________ _____________________________ _____________________________ _____________________________ _____________________________ _____________________________ ii ABSTRACT Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of three human malignancies and presents a special concern to immunocompromised individuals. Its latency-associated nuclear antigen protein (LANA) tethers latent viral genomes to host chromatin, thereby maintaining viral infection, and as such, is an attractive target for therapeutic intervention. In an effort to better understand this protein and its tethering function, we have used super-resolution microscopy to examine LANA tethers, obtaining information that remained obscured in earlier studies using standard epifluorescence microscopy. We have determined several characteristics of these tethers, including the folding properties of the underlying viral DNA and occupancy of LANA on its available viral binding sites. Quantitative data support the prediction of a coiled-coil feature in LANA dimers, and computer modeling of a minimal LANA tether illustrates the importance of viral DNA bending and nucleosome positioning on tether structure. Preliminary data examining LANA tethers during cellular mitosis suggest a potential role for mitotic machinery in manipulating tether positioning and condensation. This work also begins to address the relative timing of host chromosome condensation and LANA tether formation. These promising early results compel further study of the mitotic LANA tether and its dynamics.
  • Transcription Profile of Kaposi's Sarcoma-Associated Herpesvirus in Primary Kaposi's Sarcoma Lesions As Determined by Real-Time PCR Arrays

    Transcription Profile of Kaposi's Sarcoma-Associated Herpesvirus in Primary Kaposi's Sarcoma Lesions As Determined by Real-Time PCR Arrays

    [CANCER RESEARCH 63, 2010–2015, May 1, 2003] Advances in Brief Transcription Profile of Kaposi’s Sarcoma-associated Herpesvirus in Primary Kaposi’s Sarcoma Lesions as Determined by Real-Time PCR Arrays1 Dirk P. Dittmer2 Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104 Abstract tumor cell expresses at least one viral protein: the LANA/orf73 (2). Antibodies to LANA exist in virtually all HIV-infected as well as Kaposi’s sarcoma (KS) is the signature pathology of AIDS. KS-associ- non-HIV-infected KS patients, and other viral antigens have also been ated herpesvirus (KSHV/HHV-8) is causally linked to KS. Here, we report identified as the targets of this response. Prospective, longitudinal the first complete profile of KSHV transcription in primary KS lesions studies found that increases in peripheral blood viral load as well as using a novel, real-time PCR array. The KSHV latency I mRNAs [latency- associated nuclear antigen (LANA)/orf73, v-cyclin/orf72, and v-FLIP/ KSHV-specific antibody titers precede the onset of disease and cor- orf71] were invariably present in all biopsies. Yet, viral lytic mRNAs were relate with increased risk for KS. In addition, two lymphoproliferative detectable in only a subset of tumors. Interestingly, there was a difference disorders, primary effusion lymphoma (PEL) and multicentric Castle- in the expression pattern of the viral IFN-regulatory factors (vIRFs) man’s disease (MCD), are associated with KSHV (3, 4). These ob- encoded by KSHV. The vIRF-1/K9 clustered with LANA in KS, in con- servations imply (a) that KSHV viral oncogenes are required for KS trast to its homologue, vIRF-3/LANA-2, which is transcribed only in development and (b) that the identification of these viral genes may KSHV-associated lymphomas.
  • Inflammation and Cancer: a Comparative View

    Inflammation and Cancer: a Comparative View

    Review J Vet Intern Med 2012;26:18–31 Inflammation and Cancer: A Comparative View Wallace B. Morrison Rudolph Virchow first speculated on a relationship between inflammation and cancer more than 150 years ago. Subse- quently, chronic inflammation and associated reactive free radical overload and some types of bacterial, viral, and parasite infections that cause inflammation were recognized as important risk factors for cancer development and account for one in four of all human cancers worldwide. Even viruses that do not directly cause inflammation can cause cancer when they act in conjunction with proinflammatory cofactors or when they initiate or promote cancer via the same signaling path- ways utilized in inflammation. Whatever its origin, inflammation in the tumor microenvironment has many cancer-promot- ing effects and aids in the proliferation and survival of malignant cells and promotes angiogenesis and metastasis. Mediators of inflammation such as cytokines, free radicals, prostaglandins, and growth factors can induce DNA damage in tumor suppressor genes and post-translational modifications of proteins involved in essential cellular processes including apoptosis, DNA repair, and cell cycle checkpoints that can lead to initiation and progression of cancer. Key words: Cancer; Comparative; Infection; Inflammation; Tumor. pidemiologic evidence suggests that approximately that has documented similar or identical genetic E25% of all human cancer worldwide is associated expression, inflammatory cell infiltrates, cytokine and with chronic inflammation, chronic infection, or both chemokine expression, and other biomarkers in (Tables 1 and 2).1–5 Local inflammation as an anteced- humans and many domestic mammals with morpho- ent event to cancer development has long been recog- logically equivalent cancers.65–78 The author is una- nized in cancer patients.
  • Cancer Cause: Biological, Chemical and Physical Carcinogens

    Cancer Cause: Biological, Chemical and Physical Carcinogens

    Merit Research Journal of Medicine and Medical Sciences (ISSN: 2354-323X) Vol. 6(9) pp. 303-306, September, 2018 Available online http://www.meritresearchjournals.org/mms/index.htm Copyright © 2018 Merit Research Journals Review Cancer Cause: Biological, Chemical and Physical Carcinogens Asst. Prof. Dr. Chateen I. Ali Pambuk* and Fatma Mustafa Muhammad Abstract College of Dentistry / University of Cancer arises from abnormal changes of cells that divide without control Tikrit and are able to spread to the rest of the body. These changes are the result of the interaction between the individual genetic factors and three *Corresponding Author Email: categories of external factors: a chemical carcinogens, radiation, hormonal [email protected]. imbalance, genetic mutations and genetic factors. Genetic deviation leads to Mobile phone No. 009647701808805 the initiation of the cancer process, while the carcinogen may be a key component in the development and progression of cancer in the future. Although the factors that make someone belong to a group with a higher risk of cancer, the majority of cancers actually occur in people who do not have known factors. The aim of this descriptive mini-review, generally, is to shed light on the main cause of cancer and vital factors in cellular system and extracellular system that may be involved with different types of tumors. Keywords: Cancer, Cancer cause, physical Carcinogens, Chemical carcinogens, biological carcinogens INTRODUCTION Carcinogen is any substance (radioactive or radiation) .Furthermore, the chemicals mostly involve as the that is directly involved in the cause of cancer. This may primary cause of cancer, from which dioxins, such as be due to the ability to damage the genome or to disrupt benzene, kibon, ethylene bipromide and asbestos, are cellular metabolism or both rendering the cell to be classified as carcinogens (IUPAC Recommendations, sensitive for cancer development.
  • Visualization of Molecular Biology: the LANA Tether Vaibhav Jaina and Rolf Rennea,B,C,1

    Visualization of Molecular Biology: the LANA Tether Vaibhav Jaina and Rolf Rennea,B,C,1

    COMMENTARY COMMENTARY Visualization of molecular biology: The LANA tether Vaibhav Jaina and Rolf Rennea,b,c,1 The latency-associated nuclear antigen (LANA) plays we focus on the role of LANA with respect to ge- a central role in the biology and pathogenesis of nome persistence during latency. The first evidence Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV). that KSHV LANA, like EBNA1 from the related hu- Both classical and endemic KS in HIV-infected individ- man tumor virus Epstein–Barr virus (EBV), is re- uals and two lymphoproliferative diseases are associ- sponsibleforgenomesegregationcamein1999, ated with KSHV. During the latent phase of the viral when it was demonstrated that plasmids containing TR life cycle in dividing tumor cells, the LANA protein en- sequences were stably segregated in cells expressing sures that viral genomes persist by supporting both LANA (9, 10). Multiple groups identified the TR se- the initiation of DNA replication and segregation of quences as cis-regulatory elements essential for both viral episomes (nonintegrated circular viral genomes) the initiation of DNA replication and the segregation into daughter cells. Arguably, interrupting these com- of TR-containing plasmids during mitosis. The LANA plex LANA-dependent processes could be one of the C-terminal domain was mapped and shown to bind most promising antiviral and antitumor therapeutic to two LANA binding sites (LBS1 and LBS2) in a co- strategies. Hence, studying the molecular and cell bio- operative manner (11). Next, elegant structural and ge- logical details of LANA’s host/viral protein and chro- netic approaches demonstrated that an 18-aa-long matin interactions has been a focus in a number of N-terminal peptide specifically interacts with the H2A/ laboratories since 1996.
  • Risk Factors and Causes of Cancers in Adolescents

    Risk Factors and Causes of Cancers in Adolescents

    cancer.org | 1.800.227.2345 Risk Factors and Causes of Cancers in Adolescents A risk factor is anything that increases a person's chances of getting a disease such as cancer. Different cancers have different risk factors. In older adults, many cancers are linked to lifestyle-related risk factors such as smoking, being overweight, eating an unhealthy diet, not getting enough exercise, and drinking too much alcohol. Exposures to things in the environment, such as radon, air pollution, asbestos, or radiation during medical tests or procedures, also play a role in some adult cancers. These types of risk factors usually take many years to influence cancer risk, so they are not thought to play much of a role in cancers in children or teens. Cancer occurs as a result of changes (mutations) in the genes1 inside our cells. Genes, which are made of DNA, control nearly everything our cells do. Some genes affect when our cells grow, divide into new cells, and die. Changes in these genes can cause cells to grow out of control, which can sometimes lead to cancer. Some people inherit gene mutations from a parent that increase their risk of certain cancers. In people who inherit such a mutation, this can sometimes lead to cancer earlier in life than would normally be expected. But most cancers are not caused by inherited gene changes. We know some of the causes of gene changes that can lead to adult cancers (such as the lifestyle-related and environmental risk factors mentioned above), but the reasons for gene changes that cause most cancers in teens are not known.